We will attempt to find direct or indirect evidence of the relation of viral agents to the cause or progression of amyotrophic lateral sclerosis (ALS). We will attempt to identify and quantitate mechanisms by concurrent detailed investigations of ALS patients. These studies will be: a) clinical immunological status; b) presence of humoral and cell-mediated immune pathogenic factors as well as cytotoxic factors; c) assaying the antigenic importance of biochemical isolates of CNS materials and isolates from nerve cultures treated with ALS-CNS materials; d) assaying serum and CSF for interferon as an indicator of virus activity in addition to looking for interferon in supernates of nerve cultures treated with ALS materials. Cytotoxic activity of ALS serum for nerve cultures, if present, will serve as an in vitro model for evaluating agents that modify the toxic activity. These studies will be done concurrently by the interrelated programs with replicate samples of serum, CSF and peripheral blood cells and will be continually related to the patient's clinical activity and progress. The analysis of the various data by accepted biostatistical methods is expected to give insight into the significance of some or all of the mechanisms and this in turn will lead to agents or programs that should favorably modify this disease.